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Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD. [ABSTRACT FROM AUTHOR]

Background: Unhealthy diet is a key risk factor for Non-Communicable Diseases (NCDs) that contribute to increased morbidity and premature mortality. With increased computer literacy and mobile phone penetration, there is a high opportunity for mobile application-based interventions. The current study was conducted to develop a mobile application to monitor dietary intake and to assess its acceptability and effectiveness in diet control compared to a similar paper-based intervention. A mobile application was developed based on research evidence and opinions of local experts. The mobile application was introduced to a selected group of office workers who were in preparation, action, and maintenance stages of the Trans Theoretical Model (TTM) and a paper-based intervention was used as the comparator. Socio-demographic data were collected through a self-administered questionnaire. Participants were followed up for three months for adherence. The effectiveness of interventions was assessed at the end of three months by comparing the progressive change in the stage of change and the change from unhealthy to healthy dietary intake between two groups as primary and secondary outcomes respectively. Results: Among 123 office workers who participated in the study, 19.5% preferred the mobile intervention over the paper-based intervention. Younger, unmarried office workers and those who do not have children, had a higher acceptance for the mobile intervention (p < 0.05). There was no difference in adherence (in all three months) or outcomes between the two groups of intervention. Conclusion and recommendations: Mobile application-based interventions are better accepted among the young age group and further studies are recommended to explore their applicability. Trial registration: The study was registered in the Sri Lankan Clinical Trial Registry (Registration No. SLCTR/2020/025; Date 15th December 2020). [ABSTRACT FROM AUTHOR]

Summary This Good Practice Paper provides recommendations for the diagnosis and initial management of transplant‐eligible high‐risk myeloma patients. It describes recent updates to the genetic diagnostics of high‐risk myeloma and provides recommendations for treatment on the basis of recent prospective clinical trial evidence. [ABSTRACT FROM AUTHOR]

The apps for drawing are present in our children's life. Nevertheless, little is known about the impact of mobile technology on the freehand drawing educational activity. There are few works which are contextualised within short periods of time, with teachers who are not theirs and, in some cases, outside the children's classroom. In this paper, we are focussed on the use of technology on freehand drawing activity. Thus, we have compared the graphics produced by 4- and 5-year-old children with paper&crayon in comparison with those with tablet-finger. Children made the drawings during a planned free-drawing activity, in their ordinary classrooms, with their teachers and during five sessions. Assessment of drawings has evidenced tablet feasibility for making graphics. Nevertheless, with the passing of time, quality of graphics (tablet-finger vs paper&crayons), are nearly matched, demonstrating the low impact level technology has on this activity. In addition, if drawings are analysed specifically according to ages, results have shown that both groups have to develop adaptation strategies of visual perceptual skills and fine motor skills for the touch screen in order to obtain the same quality in the drawings made on both support types. [ABSTRACT FROM AUTHOR]

This document discusses the key concepts of translational research in the field of ophthalmology. Translational research aims to bridge the gap between existing knowledge and medical practice, with the goal of benefiting patients. It involves the transfer of diagnostic and therapeutic advances from the laboratory to clinical practice. The document explores the stakeholders of translational research, the scope of translational medicine, the components of translational research, barriers to its success, and future directions. It emphasizes the importance of collaboration and communication among different stakeholders to promote effective translational research. [Extracted from the article]

Introduction: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add‐on intervention to pharmacological treatment. AIT is a treatment with disease‐modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. Methods: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. Results: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. Conclusion: This EAACI‐PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT. [ABSTRACT FROM AUTHOR]

A high number of citations can indicate the potential of any specific paper to influence other research and generate changes in clinical practice. Analyzing the most-cited papers in a certain scientific field may assist researchers to identify the influential papers as well their main characteristics. The present study aimed to analyze the 100 most-cited papers concerning dental fluorosis (DF) through a bibliometric review. A search was performed in the Web of Science Core Collection (WoS-CC) database in November 2021. The papers were displayed in descending order according to the number of citations in WoS-CC. Two independent researchers performed the selection. Scopus and Google Scholar were used to compare the number of citations with WoS-CC. The following data were extracted from the papers: title, authors, number and density of citations, institution, country, continent, year of publication, journal title, keywords, study design, and theme. Collaborative networks were generated using the VOSviewer software. The top 100 most-cited papers were published between 1974 and 2014 and were cited 6,717 times (ranging from 35 to 417). Community Dentistry and Oral Epidemiology (24%), Journal of Dental Research (21%), Journal of Public Health Dentistry (17%), and Caries Research (13%) published the most papers. Observational studies (60%) and literature reviews (19%) were the most common study designs. The main topics were epidemiology (44%) and fluoride intake (32%). The countries with the highest number of papers were the USA (44%), Canada (10%), and Brazil (9%). The University of Iowa (USA) had the most papers (12%). Levy SM was the author with the highest number of papers (12%). The 100 most-cited papers on DF were mainly observational studies focused on epidemiology and originated in North America. There were few interventional studies and systematic reviews among the most-cited papers concerning this topic. [ABSTRACT FROM AUTHOR]

Background: Interest in and use of electronic consent (e-consent) in the conduct of academic clinical trials has increased since the COVID-19 pandemic. E-consent offers advantages including increased efficiency and accessibility, and reduced burden on site staff, which can be appealing to academic trialists anticipating challenges in recruitment to complex trial designs or with limited funding. However, there are many options to consider when using e-consent in a study protocol. This paper presents five case studies from Norwich Clinical Trials Unit, demonstrating how e-consent models can be effectively tailored to the needs of different trials. These examples illustrate the options around and benefits of e-consent, the acceptability of e-consent by participants, and the design considerations that were made during the development of the trial protocols. Case studies: Five randomised trials are presented, selected from a range of different trial designs, disease areas, interventions, and patient populations. E-consent was either offered as an alternative to paper consent, according to participant preference, or as the sole method of consent. E-consent was generally used to facilitate remote consent in decentralised trials but was also chosen to increase efficiency and reduce burden in an emergency department setting. The technical implementation of e-consent and detailed participant procedures were tailored to the needs of the trial settings and patient populations. For example, accompanying participant information sheets were provided in paper or electronic form, and electronic signatures could be typed or drawn. Administrative data on uptake of e-consent is presented where available. Conclusion: This paper demonstrates that the operational and technical aspects of implementing e-consent in clinical trials can be influenced by the trial design, the needs and characteristics of the trial population, financial/efficiency considerations, and level of risk. E-consent is not a one-size-fits-all tool for trials, and its use should be carefully considered during the development of the trial protocol, in conjunction with patient and public involvement contributors, site staff and other trial stakeholders. [ABSTRACT FROM AUTHOR]

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges. [ABSTRACT FROM AUTHOR]

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues and acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status. [ABSTRACT FROM AUTHOR]

This ENETS guidance paper, developed by a multidisciplinary working group, provides an update on the previous colorectal guidance paper in a different format. Guided by key clinical questions practical advice on the diagnosis and management of neuroendocrine tumours (NET) of the caecum, colon, and rectum is provided. Although covered in one guidance paper colorectal NET comprises a heterogeneous group of neoplasms. The most common rectal NET are often small G1 tumours that can be treated by adequate endoscopic resection techniques. Evidence from prospective clinical trials on the treatment of metastatic colorectal NET is limited and discussion of patients in experienced multidisciplinary tumour boards strongly recommended. Neuroendocrine carcinomas (NEC) and mixed neuroendocrine non‐neuroendocrine neoplasms (MiNEN) are discussed in a separate guidance paper. [ABSTRACT FROM AUTHOR]

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio – or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations. [ABSTRACT FROM AUTHOR]

The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good‐quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis‐generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death of women in the United States, yet cardiovascular research is disproportionately conducted using male human subjects and male animal models. This article deploys Katrina Hutchison's (2019) analysis of gender disparity in clinical trials as a moral aggregation problem to address the problem of underrepresentation of women in cardiovascular research. I identify cost concerns, convenience, pregnancy, and negligence as potential reasons for the underrepresentation of women in CVD research. Finally, I suggest that multilevel strategies will be needed to eliminate sex disparity in CVD research and improve patient care. [ABSTRACT FROM AUTHOR]

An editorial is presented the journal's success with an impact factor of 3.0 and offers readers an extensive collection of publications in critical care nursing research; it discusses the capabilities and limitations of large language models (LLMs) in research, presents various research articles with diverse topics and methodologies, emphasizing the use of LLMs in healthcare research, and highlights the importance of domain-specific expertise when utilizing LLMs.

The phenomenon of acute behavioral disturbance is an under-recognized and potentially life-threatening syndrome, and sometimes an emergency in psychiatric settings. Patients presenting to the Italian Emergency Departments (EDs) with acute behavioral disturbances account for approximately 3.2% of all ED visits. The spectrum of behaviors and of the signs overlaps with many clinical diseases. In addition to patients with behavioral problems related to mental disorders or substance abuse and toxicity, there is also a large group whose behavioral emergencies result from a medical illness. The complexity of these patients, as well as the interdisciplinary nature of their care, requires a clear and consensual framework for the appropriate medical management. A network of Italian scientific societies developed ten recommendations for good clinical practice. The main purpose is to draw up a document that presents a standardized method for the organization of the care of patients with acute behavioral disorders in EDs. [ABSTRACT FROM AUTHOR]

The proportion of patients with at least minimal improvement in TIS was significantly greater for those who received IVIG relative to placebo. A similar issue of emphasis on patients with muscle involvement arises in using TIS as the primary outcome measure. These results led to US Food and Drug Administration (FDA) approval of IVIG use in treating DM. [Extracted from the article]

Background: There is an often-held assumption that the engagement of clinicians and healthcare organizations in research improves healthcare performance at various levels. Previous reviews found up to 28 studies suggesting a positive association between the engagement of individuals and healthcare organizations in research and improvements in healthcare performance. The current study sought to provide an update. Methods: We updated our existing published systematic review by again addressing the question: Does research engagement (by clinicians and organizations) improve healthcare performance? The search covered the period 1 January 2012 to March 2024, in two phases. First, the formal updated search ran from 1 January 2012 to 31 May 2020, in any healthcare setting or country and focussed on English language publications. In this phase two searches identified 66 901 records. Later, a further check of key journals and citations to identified papers ran from May 2020 to March 2024. In total, 168 papers progressed to full-text appraisal; 62 were identified for inclusion in the update. Then we combined papers from our original and updated reviews. Results: In the combined review, the literature is dominated by papers from the United States (50/95) and mostly drawn from the Global North. Papers cover various clinical fields, with more on cancer than any other field; 86 of the 95 papers report positive results, of which 70 are purely positive and 16 positive/mixed, meaning there are some negative elements (i.e. aspects where there is a lack of healthcare improvement) in their findings. Conclusions: The updated review collates a substantial pool of studies, especially when combined with our original review, which are largely positive in terms of the impact of research engagement on processes of care and patient outcomes. Of the potential engagement mechanisms, the review highlights the important role played by research networks. The review also identifies various papers which consider how far there is a "dose effect" from differing amounts of research engagement. Additional lessons come from analyses of equity issues and negative papers. This review provides further evidence of contributions played by systems level research investments such as research networks on processes of care and patient outcomes. [ABSTRACT FROM AUTHOR]

Background Aims Methods Main Contribution Conclusions WHAT THIS PAPER ADDS What is already known on the subject What this paper adds to existing knowledge What are the clinical implications of this work? Communication impairments are a leading concern for parent caregivers of individuals with rare neurodevelopmental disorders (RNDDs). Clinical trials of disease modifying therapies require valid and responsive outcome measures that are relevant to individuals with RNDDs. Identifying and evaluating current psychometric properties for communication measures is a critical step towards the selection and use of appropriate instruments.This systematic review offers (1) a description of parent‐reported communication measures and (2) evidence for their psychometric properties, in RNDDs.The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022334649). MEDLINE (Ovid), Embase, PsychINFO, Web of Science, CINAHL Plus, Cochrane Library, ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry were searched from inception to August 2023. Methodological assessment of quality was completed using the COnsensus‐based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Parent‐reported measures used in observational studies and clinical trials were identified. Data on utility, reliability and validity for RNDDs were extracted.Sixteen parent‐reported communication measures were used in RNDD research, the Vineland Adaptive Behavior Scales being most commonly used. Validation data in RNDDs were identified for six of these measures. Limitations related to sample size or the scope of psychometric testing.Many communication measures have been used for RNDDs but there are few data validating their use. Valid and reliable methods of measuring communication in persons with RNDDs is a priority for future high‐quality clinical trials. Communication is a critical domain for families with a child with a rare neurodevelopmental disorder (RNDD). Validated outcome measures are essential for accurate evaluation and interpretation of responses to treatments in clinical trials. We identified 16 parent‐reported communication measures that have been used with RNDDs, but only six measures had validation data for at least one RNDD. High quality evidence is accumulating, with all validation studies in this review published between 2020 to 2023. Modifications of existing measures may be required to assess communication for RNDDs. This systematic review catalogues the available psychometric data for communication measures and indicates an ongoing need for new validation studies to ensure they are fit‐for‐purpose for upcoming clinical trials in RNDDs. This review will inform the selection of communication measures for clinical trials and research studies. [ABSTRACT FROM AUTHOR]

In silico clinical trials (ISCTs) are an emerging method in modeling and simulation where medical interventions are evaluated using computational models of patients. ISCTs have the potential to provide cost-effective, time-efficient, and ethically favorable alternatives for evaluating the safety and effectiveness of medical devices. However, ensuring the credibility of ISCT results is a significant challenge. This paper aims to identify unique considerations for assessing the credibility of ISCTs and proposes an ISCT credibility assessment workflow based on recently published model assessment frameworks. First, we review various ISCTs described in the literature, carefully selected to showcase the range of methodological options available. These studies cover a wide variety of devices, reasons for conducting ISCTs, patient model generation approaches including subject-specific versus 'synthetic' virtual patients, complexity levels of devices and patient models, incorporation of clinician or clinical outcome models, and methods for integrating ISCT results with real-world clinical trials. We next discuss how verification, validation, and uncertainty quantification apply to ISCTs, considering the range of ISCT approaches identified. Based on our analysis, we then present a hierarchical workflow for assessing ISCT credibility, using a general credibility assessment framework recently published by the FDA's Center for Devices and Radiological Health. Overall, this work aims to promote standardization in ISCTs and contribute to the wider adoption and acceptance of ISCTs as a reliable tool for evaluating medical devices. Author summary: A new method for evaluating a medical device is an in silico clinical trial, where the device performance is tested using computational models representing a cohort of patients. Demonstrating that in silico clinical trials are reliable is clearly of paramount importance. However, little information is available on how to ensure this. In this paper we present a workflow for evaluating an in silico clinical trial. This workflow was developed by considering a wide-ranging sample of previously published in silico clinical trials, together with a detailed assessment of how specific model evaluation activities apply to in silico clinical trials. [ABSTRACT FROM AUTHOR]

Conceptualizing tobacco dependence as a chronic relapsing condition suggests the need to use analytic strategies that reflect that premise. However, clinical trials for smoking cessation typically define the primary endpoint as a measure of abstinence at a single timepoint distal to the intervention, typically 3–12 months. This reinforces the concept of tobacco outcomes as a dichotomous state—one is, or is not, abstinent. Fortunately, there are several approaches available to handle longitudinal data that reflect the relapsing and remitting nature of tobacco use during treatment studies. In this paper, sponsored by the Society for Research on Nicotine and Tobacco's Treatment Research Network, we present an introductory overview of these techniques and their application in smoking cessation clinical trials. Topics discussed include models to examine abstinence outcomes (eg, trajectory models of abstinence, models for transitions in smoking behavior, models for time to event), models that examine reductions in tobacco use, and models to examine joint outcomes (eg, examining changes in the use of more than one tobacco product). Finally, we discuss three additional relevant topics (ie, heterogeneity of effects, handling missing data, and power and sample size) and provide summary information about the type of model that can be used based on the type of data collected and the focus of the study. We encourage investigators to familiarize themselves with these techniques and use them in the analysis of data from clinical trials of smoking cessation treatment. Implications Clinical trials of tobacco dependence treatment typically measure abstinence 3–12 months after participant enrollment. However, because smoking is a chronic relapsing condition, these measures of intervention success may not accurately reflect the common trajectories of tobacco abstinence and relapse. Several analytical techniques facilitate this type of outcome modeling. This paper is meant to be an introduction to these concepts and techniques to the global nicotine and tobacco research community including which techniques can be used for different research questions with visual summaries of which types of models can be used for different types of data and research questions. [ABSTRACT FROM AUTHOR]

Biostatistics plays a pivotal role in developing, interpreting and drawing conclusions from clinical, biological and epidemiological data. However, the improper application of statistical methods can lead to erroneous conclusions and misinterpretations. This paper provides a comprehensive examination of the most frequent mistakes encountered in the biostatistical analysis process. We identified and elucidated 10 common errors in biostatistical analysis. These include using the wrong metric to describe data, misinterpreting P -values, misinterpreting the 95% confidence interval, misinterpreting the hazard ratio as an index of prognostic accuracy, ignoring the sample size calculation, misinterpreting analysis by strata in randomized clinical trials, confusing correlation and causation, misunderstanding confounders and mediators, inadequately codifying variables during the data collection, and bias arising when group membership is attributed on the basis of future exposure in retrospective studies. We discuss the implications of these errors and propose some practical strategies to mitigate their impact. By raising awareness of these pitfalls, this paper aims to enhance the rigor and reproducibility of biostatistical analyses, thereby fostering more robust and reliable biomedical research findings. [ABSTRACT FROM AUTHOR]

Background: This study examines the effect of a Theory of Mind (ToM) intervention on ToM abilities and social–emotional functioning in adolescents with developmental language disorder (DLD) or who are deaf/hard of hearing (D/HH). It emphasizes the importance of self‐reflection and measurement for personal growth. The research design incorporates both subjective and objective measures to evaluate the intervention's efficacy. Aims: To investigate the impact of the ToM intervention on ToM abilities and social–emotional functioning in adolescents with DLD or who are D/HH. It hypothesizes that participants in the intervention groups will show improved ToM and social–emotional functioning compared with those in the control groups. Methods & Procedures: Adolescents with DLD or who are D/HH were recruited through collaboration with educational institutions. The study utilized a pre‐/post‐test design, assigning participants to either the intervention or the control group. The ToM intervention involved targeted activities to enhance ToM abilities. ToM abilities and social–emotional functioning were assessed using standardized tests and self‐report questionnaires. Statistical analyses compared outcomes between the intervention and no intervention groups. Outcomes & Results: The findings reveal subjective improvements in social–emotional functioning among the D/HH intervention group. However, no significant effects on objective ToM measures were observed. These results highlight the need for further investigation and refinement of interventions in these areas. Future research should focus on improving intervention strategies and exploring additional objective measures to gain a comprehensive understanding of the intervention's impact on ToM and social–emotional functioning in this population. Conclusions & Implications: The ToM intervention shows subjective benefits in improving social–emotional functioning among D/HH adolescents. However, it does not yield significant effects on objective ToM measures. These findings emphasize the ongoing need to refine interventions targeting ToM abilities and social–emotional functioning in this population. Future studies should explore alternative strategies and incorporate additional objective measures to enhance understanding and outcomes. WHAT THIS PAPER ADDS: What is already known on this subject: Before this study, it was known that ToM interventions have the potential to enhance ToM abilities. However, the specific effects of such interventions on subjective and objective measures for ToM and social–emotional functioning in adolescents with DLD or who are D/HH remained unclear, necessitating further research. What this paper adds to the existing knowledge: This study adds to the existing knowledge by demonstrating subjective improvements in social–emotional functioning among adolescents who are D/HH and underwent a ToM intervention. However, no significant effects on objective ToM measures were observed. These findings highlight the need for refining interventions and exploring additional measures to better understand the intervention's impact. What are the potential or actual clinical implications of this work?: The subjective improvements in social–emotional functioning observed in this study have important clinical implications. They suggest that ToM interventions can positively impact the social well‐being of adolescents who are D/HH. However, the lack of significant effects on objective ToM measures emphasizes the need for further research and intervention refinement to address specific areas of improvement in this population. [ABSTRACT FROM AUTHOR]

JAMA: Journal of the American Medical Association has published a Special Communication titled "The Integration of Clinical Trials With the Practice of Medicine: Repairing a House Divided," which discusses the need to integrate clinical trials with clinical practice. The authors highlight the separate missions and infrastructures of clinical trialists and clinicians, leading to inefficiencies and limitations in trials. They propose solutions such as implementation science, novel statistical analysis approaches, and integration of trials with electronic health records. JAMA is launching a new series called "Integrating Clinical Trials and Practice" to explore innovations in trial design, funding, regulation, education, and application. The goal is to align clinical trials with clinical practice and improve patient care. [Extracted from the article]

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management. [ABSTRACT FROM AUTHOR]

The application of STEM (Science, Technology, Engineering, and Math) education in solving real-world problems is challenging. To tackle this challenge, a project-based learning approach that integrates robots with cost-effective self-made toys to problem-solving was adopted to assist rural primary school students to apply STEM skills. The purpose of this study was to evaluate the effects of the project-based learning approach which includes lecturing and hands-on activities on primary school students' STEM learning outcomes and attitudes. An experiment was conducted with 25 primary school students who voluntarily participated in a STEM summer-camp programme. Students were asked to assemble a paper house equipped with an IoT control module and LED light switches, and write and edit robot scripts to produce a robot-based storytelling narrative using the paper house they made as a context. The results show that the project-based learning approach was an effective approach for cultivating primary school students' STEM knowledge and skills as evidenced from the post-written test. The relationships between the students' STEM learning outcomes and attitudes were also confirmed by a clustering analysis. Students who had higher learning attitudes also achieved higher STEM learning outcomes; the findings are also supported by the feedback from the open-ended questionnaire items. This study suggests that integrating low-cost self-made toys and robots in project-based learning activities is an effective and practical approach to enhance primary school students' learning outcomes and learning attitudes in STEM education. [ABSTRACT FROM AUTHOR]

Clinical trials are very important for determining the safety and efficacy of medical trials, which is further critical to the progress of the various healthcare businesses. Conducting such studies requires substantial preparation and adherence to the various ethical norms; such norms which are especially crucial when dealing with medical emergencies like the COVID-19 outbreak. This paper discusses the Site Initiation Visit (SIV) and the development of Essential Document Files (EDF) for clinical research. Site initiation visit specifies fundamental tasks to ensure team preparedness, logistical planning, and regulatory compliance. Team training, investigational product (IP) storage, and post-SIV follow-up procedures are all valuable considerations. On the other hand, throughout the trial's lifecycle, the document files play a very vital role in ensuring a complete documentation process thereby promoting transparency and adherence to Good Clinical Practice (GCP) guidelines. The paper highlights the importance of established protocols and regulatory compliance, in safeguarding safety by outlining these procedures. [ABSTRACT FROM AUTHOR]

Complex and enduring mental health problems require greater treatment resources, usually in the form of multidisciplinary support, including providing psychological therapies. This paper reports on an NHS, tertiary-level specialist psychotherapy service offering Psychodynamic therapies with longer-term, exploratory transdiagnostic approaches to support complexity and sustained personality functioning. This paper adopts a naturalistic study design evaluating the effectiveness of Psychodynamic therapy using pre- and post-outcomes across a 10-year period. A total of n = 474 participants self-report pre- and post-outcome measures were used as the marker of effectiveness along with therapist assessments during intake and engagement. The findings showed that Psychodynamic therapy was effective in reducing psychological distress based on service-user self-report and therapist assessments. While intake scores varied by socio-demographic factors, the rate of change across most groups was similar. There were several limitations relating to data quality and completeness which reflect the naturalistic design. Despite the limits of a naturalistic design, this study provides evidence of support for the place of Psychodynamic therapies within NHS mental health care, catering to those with complex and enduring mental health problems. [ABSTRACT FROM AUTHOR]

Background: A skin tear is a traumatic wound that occurs in up to one in five hospitalized patients. Nursing care includes application of a dressing to create a moist wound healing environment. Aim: To compare the effectiveness of two standard dressings (adhesive silicone foam vs. meshed silicone interface) to heal hospital‐acquired skin tear. Methods: An intention‐to‐treat pilot study was designed using a randomized, non‐inferiority trial in an Australian tertiary hospital setting. Consenting participants (n = 52) had acquired a skin tear within the previous 24 h and had agreed to a 3‐week follow‐up. Data were collected between 2014 and 2020. The primary outcome measure was wound healing at 21 days. Results: Baseline characteristics were similar in both arms. Per protocol, 86% of skin tears were fully healed at 3 weeks in the adhesive silicone foam group, compared to 59% in the meshed silicone interface group. Greater healing was observed across all skin tear categories in the adhesive silicone foam dressing group. In the intention‐to‐treat sample, healing was 69% and 42%, respectively. Conclusions: Results suggest the adhesive silicone foam dressing may be superior, as it produced clinically significant healing of skin tears at 3 weeks compared to the meshed silicone interface dressing. Accounting for potential loss to follow‐up, a sample of at least 103 participants per arm would be required to power a definitive study. Summary statement: What is already known about this topic? A skin tear is a traumatic wound that is commonly acquired during hospitalization that affects older adults in particular. In hospital settings, it may occur in up to one in five patients.A variety of skin tear dressings have been used in previous studies, with healing rates ranging from 34% to 97% at 21 days; however, evidence for the most effective dressing type is inconclusive.If treated inappropriately, or left untreated, minor skin tears can become chronic or complicated wounds, yet prevalence and treatment of hospital‐acquired injuries are under‐reported. What this paper adds? Based on our per‐protocol results, an adhesive silicone foam dressing may be superior, as it produced clinically significant healing of 86% of skin tears at 3 weeks compared to 59% with the meshed silicone interface dressing.Based on the methods and results from this pilot study, a future definitive trial would be feasible but would need to account for a relatively large loss to follow‐up rate. The implications of this paper: Using our intention‐to‐treat results, a future study would need a sample size of 103 per arm to be sufficiently powered, which may be impractical to achieve within a single hospital setting; thus, a multi‐site study would be advisable. [ABSTRACT FROM AUTHOR]

Background: The prevalence of sexually transmitted diseases (STDs) remains high worldwide in today's society, especially among young people. Youth education on STDs could help to reduce the prevalence of the condition in society and prevent new cases. Aim: The aim of this study is to assess the effectiveness of peer‐based short‐form educational videos on youths' knowledge of STDs. Methods: This quasi‐experimental study was conducted in Turkey. The sample consisted of 121 students divided into experimental and control groups. Pre‐ and post‐test control group quasi‐experimental research design was employed in this study during the spring semester of the academic year 2021–2022. Peer‐based short‐form educational videos created by nursing students were used as an intervention. The survey form and Sexually Transmitted Disease Knowledge Questionnaire were used to collect data. Results: Participants with parental responsibilities and had previous STD experience had higher knowledge score than the other subgroups. There was a significant main effect of peer‐based short‐form educational video on participants overall knowledge score of STDs. Additionally, the effect of intervention continued at 12‐week follow‐up measurement. Conclusion: Peer‐based short‐form educational videos increase young people's knowledge of STD, and the impact of the intervention continued at 12‐week follow up. Summary statement: What is already known about this topic? Sexually transmitted diseases continue to be prevalent in society, particularly among young people.Sexually transmitted diseases can lead to serious health conditions and have a significant impact on sexual and reproductive health.The effectiveness of internet‐based education and lectures on sexually transmitted diseases has already been investigated.Little research has been addressed to determine the impact of educational materials, which are short videos on knowledge of sexually transmitted diseases created by utilizing nursing students' peer assessment. What this paper adds? Peer‐based short‐form educational videos increase young people's sexually transmitted disease knowledge.People with parental responsibilities and a previous sexually transmitted infections responded to interventions more favourably.The effects of peer‐based short‐form educational videos persisted 3 months afterwards. The implications for this paper: This cost‐free method has a potential to be widely used as a public health intervention to educate young people on sexually transmitted diseases.The peer‐based short‐form educational videos can be combined with other interventions to increase young people's knowledge of sexually transmitted diseases. [ABSTRACT FROM AUTHOR]

The quality of the very early emotional experiences in a child's life are recognized today as foundational in the mental health of becoming an adult. Unsurprisingly, clinicians and health authorities agree on the importance of early detection and treatment of any mental health issues experienced by the preschool child. This is even more important and challenging as young children do not yet have the language skills necessary to express their distress. But do the caregivers in charge of these populations have the best tools at their disposal to carry out that important mission in an efficient and scientifically robust manner reflecting the latest research findings and scientific literature? This is the question we try to answer in this paper. We revisited the theoretical underpinnings behind the concept of mentalization as playing a key role in the ability to understand the other's inner reality. We then carried out an extensive review of scientific papers written over the past 30 years on the subject. We examined mental representations of the adult on the child and analyzed those mentalizations as key inputs. We focused on extracting cross analyses of the mentalizations of one child by several adults with different functions in the life of the child. In this process, we used the PRISMA methodology applied to large international medical databases. We found that the qualitative approach, usually associated with a lengthy process, has been overwhelmingly used in trying to assess patients' mental states and to analyze the mentalizations on the patient, adult or child. Furthermore, cross analyses of mentalizations from more than one adult on a given child were almost nonexistent, despite having high epistemic and clinical potential. There is a dearth of reliable quantitative tools, able to capture and analyze the mentalizations on a patient, that are scientifically robust, transposable, and easy to implement in a clinical setting. The absence of such tools for medical professionals in charge of assessing preschool children contributes, in our view, the low detection and poor treatment of mental disorders in that particularly vulnerable population. We believe there is here an urgent unmet need and that such tools should be designed, validated, and deployed into the target populations as early as possible. [ABSTRACT FROM AUTHOR]

Background: The lack of a clear answer regarding the efficacy of physiotherapy in the treatment of cubital tunnel syndrome (CuTS) has led to attempts to critically assess the scientific studies conducted to date. Materials and Methods: Two databases (MEDLINE via PubMed and PEDro) and Google Scholar were used to search for papers. The inclusion criteria were randomized controlled trials, case series, and case reports that evaluate the effects of physiotherapy in the treatment of patients with CuTS. Results: A total of 18 studies met the eligibility criteria, capturing a total of 425 participants. Seven papers were randomized controlled trials, three more described prospective studies without a control group, and eight papers contained case reports. An analysis of the literature evaluating the effectiveness of various forms of broadly defined physiotherapy indicates that their use can have a beneficial effect in reducing many subjective and objective symptoms and improving function. In the majority of papers included in this review, their authors indicated positive therapeutic effects. Only one randomized controlled trial reported no change following therapy. It can therefore be stated that the results of the research conducted so far are optimistic. However, only 7 of the 18 papers were randomized controlled trials, while 3 were prospective studies, and 8 papers were case studies, in which 23 people with CuTS were studied. Conclusions: The small number of randomized clinical trials and their considerable heterogeneity do not allow firm conclusions to be drawn about the effectiveness of physiotherapy in the conservative treatment of CuTS. [ABSTRACT FROM AUTHOR]

Background: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. Methods: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. Results: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. Conclusions: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs. [ABSTRACT FROM AUTHOR]

Background/aims: The value of using qualitative methods within clinical trials is widely recognised. How qualitative research is integrated within trials units to achieve this is less clear. This paper describes the process through which qualitative research has been integrated within Cardiff University's Centre for Trials Research (CTR) in Wales, UK. We highlight facilitators of, and challenges to, integration. Methods: We held group discussions on the work of the Qualitative Research Group (QRG) within CTR. The content of these discussions, materials for a presentation in CTR, and documents relating to the development of the QRG were interpreted at a workshop attended by group members. Normalisation Process Theory (NPT) was used to structure analysis. A writing group prepared a document for input from members of CTR, forming the basis of this paper. Results: Actions to integrate qualitative research comprised: its inclusion in Centre strategies; formation of a QRG with dedicated funding/roles; embedding of qualitative research within operating systems; capacity building/training; monitoring opportunities to include qualitative methods in studies; maximising the quality of qualitative research and developing methodological innovation. Facilitators of these actions included: the influence of the broader methodological landscape within trial/study design and its promotion of the value of qualitative research; and close physical proximity of CTR qualitative staff/students allowing sharing of methodological approaches. Introduction of innovative qualitative methods generated interest among other staff groups. Challenges included: pressure to under-resource qualitative components of research, preference for a statistical stance historically in some research areas and funding structures, and difficulties faced by qualitative researchers carving out individual academic profiles when working across trials/studies. Conclusions: Given that CTUs are pivotal to the design and conduct of RCTs and related study types across multiple disciplines, integrating qualitative research into trials units is crucial if its contribution is to be fully realised. We have made explicit one trials unit's experience of embedding qualitative research and present this to open dialogue on ways to operationalise and optimise qualitative research in trials. NPT provides a valuable framework with which to theorise these processes, including the importance of sense-making and legitimisation when introducing new practices within organisations. [ABSTRACT FROM AUTHOR]

Simple Summary: Metformin is one of the most widely used drugs in the world, since its first use in the second part of the 1950s in France (Aron, 1957) and in the United Kingdom (Rona, 1958), and is on the World Health Organization's List of Essential Medicines. Traditionally, metformin is used in diabetes mellitus, mainly in overweight and obese subjects, but also in other conditions of impaired glucose metabolism, such as insulin resistance. In recent years, in vitro and in vivo data on this molecule as an antiproliferative modulator have suggested a series of clinical trials in several tumors that—at the moment—have not confirmed the expected positive results. The aim of this paper is to offer a double vision of this molecule, with a very light side about the metabolic aspects and a darker side concerning its antineoplastic activity, focusing on molecular and subcellular pathways involved in both fields and discussing the contrast between preliminary cellular data and real clinical outcomes in different neoplasms. The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open? [ABSTRACT FROM AUTHOR]

Background and Objectives: Chloroquine and its analog hydroxychloroquine are derivatives of 4-aminoquinoline and are regularly used in the treatment of malaria and autoimmune diseases. Among the side effects of these drugs, alterations associated with the auditory system are frequently mentioned. Thus, the aim of this systematic review is to systematically review publications on hearing disorders and chloroquine or hydroxychloroquine use. Materials and Methods: Inclusion criteria were observational or interventional studies on audiological assessment in participants who were using chloroquine or hydroxychloroquine. The methodological quality was independently assessed by two reviewers using the Meta-Analysis of Statistics: assessment and review Instrument. The certainty of the evidence was assessed using the GRADE tool. Results: A total of 1,372 non-duplicate papers were screened, out of which 17 were included in the final qualitative synthesis, and 5 studies in the meta-analysis. The odds ratio for the two subgroups evaluated did not show significance with no heterogeneity between the effects observed between the different diseases (I²=0%) and obtaining the global estimate of 0.76 (95% confidence interval [CI]=0.41-1.39; p>0.05). Despite the inclusion of papers with different disease samples, the heterogeneity observed in the analysis was low (I²= 0%) and prediction interval (95% PI=0.32-1.80; p>0.05) remained close to that estimated by the CI (95% CI=0.41-1.39; p>0.05). The certainty of the evidence assessed by the GRADE tool was considered very low due to the risk of bias, indirect evidence, and imprecision. Conclusions: The findings of this study suggest that the use of chloroquine/hydroxychloroquine is not associated with hearing disorders. [ABSTRACT FROM AUTHOR]

The lack of ideal measurement of treatment efficacy is a well acknowledged problem in the epilepsy community, both in clinical care and clinical trials. Whilst still the current gold-standard, self-reported seizure frequency significantly underestimates the true number of seizures and does not account for any other at least equally important outcome parameters, such as neurodevelopment and cognition. With the rise of disease modifying treatments, the need for more reliable endpoints in practice and clinical trials becomes more pressing. In this paper we assembled an expert panel to discuss the nature of these needs, current limitations, and obstacles based on a survey amongst these experts who were queried about the most important issues regarding the use of electroencephalography (EEG) parameters as endpoints in clinical drug and device development. A structured survey was sent to a group of experts in the design and conduct of epilepsy trials in adults and children. This was followed by a virtual in-person meeting discussing the results of the trial and identifying a list of most important issues. Six clinical trialists and 5 individuals from pharmaceutical companies returned the survey containing 14 questions, and 8 clinical trialists and 10 pharma-representatives attended the meeting. Three main issues were identified (1) lack of accuracy of seizure diaries due to nocturnal seizures, subtle motor seizures, impairment of consciousness and lack of awareness of the seizure by the patient (2) inter-rater variability of EEG assessment (3) lack of standardization regarding definition(s) of seizures (clinical and electrographic), EEG recording methods and EEG data management. Recommended solutions included (1) validation of EEG parameters as biomarkers and use of wearables (2) development of a manual that describes EEG rating criteria, protocol for validation by > 1 central reader and use of a resolution of disagreements reporting template (3) standardization of EEG recording, data management and reporting. Current developments in research and technology seem promising to advance the use of EEG parameters as potential endpoints and offer partial solutions to the current needs. However, continuous, focused and collaborative efforts of all stakeholders (academia, industry and regulatory agencies) are needed to formulate guidelines, validate emerging technologies and approve them for use in trials. It is the intent of this opinion "position paper" to stimulate those efforts. • Multiple potential EEG are parameters known and some already used. • EEG parameters must be selected to address a specific question. • Due to significant heterogeneity of seizure types, syndromes, the use of EEG will vary according to purpose. • Evidence is required to "validate" the utility of a specific measure to a specific question before use in a trial. [ABSTRACT FROM AUTHOR]

Background: Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed. Methods: As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings. Outcome. Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities. Conclusion: Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings. [ABSTRACT FROM AUTHOR]

The International Union of Basic and Clinical Pharmacology (IUPHAR) Geriatric Committee aims to improve the use of drugs in older adults and develop new therapeutic approaches for the syndromes and diseases of old age through advocacy, education, and research. In the present paper, we propose strategies relevant to drug development and evaluation, spanning preclinical and the full range of clinical studies. Drugs for older adults need to consider not only age, but also other characteristics common in geriatric patients, such as multimorbidity, polypharmacy, falls, cognitive impairment, and frailty. The IUPHAR Geriatric Committee's position statement on 'Measurement of Frailty in Drug Development and Evaluation' is included, highlighting 12 key principles that cover the spectrum of translational research. We propose that where older adults are likely to be major users of a drug, that frailty is measured at baseline and as an outcome. Preclinical models that replicate the age, frailty, duration of exposure, comorbidities, and co‐medications of the proposed patients may improve translation. We highlight the potential application of recent technologies, such as physiologically based pharmacokinetic–pharmacodynamic modeling informed by frailty biology, and Artificial Intelligence, to inform personalized medicine for older patients. Considerations for the rapidly aging populations in low‐ and middle‐income countries related to health‐care and clinical trials are outlined. Involving older adults, their caregivers and health‐care providers in all phases of research should improve drug development, evaluation, and outcomes for older adults internationally. [ABSTRACT FROM AUTHOR]

The validity of driving simulators is a topic that has been addressed ever since their first use. In practice, a comparison of field data and simulator data is often used for validation purposes. A systematic literature search was conducted which identified large heterogeneity in both study designs and statistical methods used in research on simulator validity. Most of the included studies concluded simulator validity (thus equivalence of field data and simulator data) from non-significant results in Null-Hypothesis Significance Testing (NHST), which is a well-known yet somewhat controversial practice. In this work, the consequences of both study design choice and the choice of the statistical method are outlined and alternatives such as using Bayes factor hypothesis testing and equivalence tests are discussed and applied to a real data example. The present paper is intended to shed light on the influence of the statistical method on conclusions drawn from experimental data. For research on driving simulator validity, we highly encourage the use of equivalence tests or Bayes factor hypothesis tests, in particular when evidence of the data suggests that an effect might be absent. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there is no consensus regarding the management of intermittent exotropia (IXT), which includes both surgical and non-surgical treatment options. Nonsurgical management of IXT has been suggested and includes watchful observation, patching, overminus lenses, prism, and vision therapy/orthoptics. While a significant portion of IXT patients are treated by surgery, it is reported that there is a substantial tendency for reoperation or recurrence of IXT. This paper provides a comprehensive review of non-surgical and surgical treatment options for the IXT. Methods: Search strategies involving combination of keywords including intermittent exotropia, divergence excess, basic exotropia, refractive error, glasses, spectacles, natural history, untreated, observe, occlusion, patch, overminus, overcorrecting minus, prism, vision therapy, orthoptic, anti-suppression, fusion exercise, and surgery were used in Medline. All English articles from 01/01/1900 to 01/09/2020 were reviewed. The reference list of the identified articles was also checked for additional relevant articles. Studies focused on animal models or strabismus associated with neurologic disorders or injury were excluded. The following filters were used for surgical management due to the abundance of reports: full text, randomized controlled trial, review, in the last 5 years. Results: Appropriate optical correction of refractive error is generally the starting point for all management approaches, but there is a lack of randomized clinical trial data regarding this treatment modality. Randomized clinical trial data indicate that both observation and occlusion are reasonable management options for children 3–10 years old, and there were insufficient data to recommend occlusion for children 12–35 months old. While overminus lenses were found to improve the control of IXT when assessed wearing overminus spectacles, this improvement did not persist after the treatment ended. The result of the only randomized clinical trial on the effectiveness of base-in prism indicated that this treatment is no more effective than nonprism spectacles for improving control. A recent randomized clinical trial showed that vision therapy/orthoptics is effective in improving the control of IXT when compared to observation alone. Surgery was found to alter a number of clinical characteristics of IXT, including reducing the distance and near angle of deviation, reducing photophobia, improving health-related quality of life, stereopsis, and the Newcastle Control Score. However, there are no randomized clinical trial data comparing surgery with a control group such as placebo or a no treatment observation group. Discussion: Rigorously designed clinical trials to investigate the effectiveness of non-surgical and surgical treatments for intermittent exotropia are needed. [ABSTRACT FROM AUTHOR]

Background: The incidence of coagulation of continuous renal replacement therapy circuits remains high. To the best of our knowledge, no scholar has published a protocol to avoid management errors when different types of citrates coexist in the same Intensive Care Unit. Aim: To assess the safety and efficacy of the unification of two protocols with different concentrations of citrate solution. Study Desing: A prospective, quasi‐experimental study was carried out in the intensive care unit of a tertiary referral hospital (in Barcelona, Spain), over 3 years. Consecutive adult patients requiring continuous renal replacement therapy with citrate were included. The sample was divided into two groups, a control group (concentrated citrate) and an intervention group (diluted citrate). The decision to initiate anticoagulation with diluted (18 mmol/L) or concentrated (136 mmol/L) citrate was made based on the machine available and the decision of the doctor responsible for the patient. It was not possible to randomize the sample. Both protocols were matched with a starting citrate dose of 3.5 mmol/L, and a dialysis solution was used. Post‐filter replacement was not used, and the citrate solution was the only fluid administered pre‐filter. Results: The analysis included 59 circuits in the concentrated citrate group and 40 circuits in the diluted citrate group. An increased need for electrolyte replacement was observed in the diluted group (p <.001). The concentrated citrate group had a longer filter life (p <.05), and there was a slight trend toward alkalosis. Conclusion: The diluted citrate group had a higher incidence of electrolyte replacement. The concentrated citrate group had longer circuit lifespan and a trend toward metabolic alkalosis, although this was not statistically significant. If these conclusions are considered, the protocol can be unified. Relevance to Clinical Practice: The present work aims to provide information on the differences in the use of regional anticoagulation with diluted or concentrated citrate. The objective is to pay special attention to aspects that can lead to complications. The unified protocol proposed in this paper could be extrapolated to any machine on the market that uses either of these two types of citrate concentration. [ABSTRACT FROM AUTHOR]

Dysregulated JAK/STAT hyperactivity is essential to the pathogenesis of myelofibrosis, and JAK inhibitors are the first-line treatment option for many patients. There are four FDA-approved JAK inhibitors for patients with myelofibrosis. Single-agent JAK inhibition can improve splenomegaly, symptom burden, cytopenias, and possibly survival in patients with myelofibrosis. Despite their efficacy, JAK inhibitors produce variable or short-lived responses, in part due to the large network of cooperating signaling pathways and downstream targets of JAK/STAT, which mediates upfront or acquired resistance to JAK inhibitors. Synergistic inhibition of JAK/STAT accessory pathways can increase the rates and duration of response for patients with myelofibrosis. Two recently reported, placebo-controlled phase III trials of novel agents added to JAK inhibition met their primary endpoint, and additional late-stage studies are ongoing. This paper will review role of dysregulated JAK/STAT signaling, biological plausible additional therapeutic targets and the recent advancements in combination strategies with JAK inhibitors for myelofibrosis. [ABSTRACT FROM AUTHOR]

Objective: The concept of self-efficacy is a determining factor in many behaviours related to health promotion and health education. Several pilot studies have been conducted in different parts of the world on different populations regarding the impact of training based on the Pender Health Promotion Model on self-efficacy, yielding conflicting results. Therefore, the present systematic review and meta-analysis were conducted with the aim of evaluating and summarizing the results of studies on the impact of training based on the Pender Health Promotion Model on self-efficacy. Data Source: MagIran, SID, PubMed, Embase, Web of Science (WoS), Scopus and Google Scholar. Study Inclusion and Exclusion Criteria: Original scientific research articles; Interventional studies; Studies investigating the effects of education based on the Pender Health Promotion Model on self-efficacy; Studies irrelevant to the objective; Cross-sectional studies; case reports; and papers presented in conferences; letters to the editor; systematic and meta-analysis studies. Data Extraction: Two independent reviewers extracted data and assessed the quality of the 18 included studies using a pre-prepared checklist for the systematic review and meta-analysis process. Data Synthesis: We conducted meta-analyses and reported the characteristics, outcomes, and risk of bias of studies. Methods: The present study was conducted according to PRISMA guidelines until December 2022. The quality assessment of the included articles for meta-analysis was performed using the JBI checklist. Heterogeneity of the studies was calculated using the I 2 statistics, and Egger's regression intercept was used to assess publication bias. Results: In the initial search, 13,943 studies were found, and after excluding studies irrelevant to the research objective, a total of 18 articles were included in the meta-analysis. These articles represented a sample size of 1015 individuals in the intervention group and 999 individuals in the control group. The combined results of the studies showed a significant increase in self-efficacy in the intervention group when compared to the control group (1.788 ±.267; CI: 95%, P <.001). With an increase in the year of study and the quality assessment score of the articles, the effect of the intervention decreased (P <.001). Conclusion: The results of this study indicated that training based on the Pender Health Promotion Model significantly increased self-efficacy. Therefore, it seems that training based on this model can have positive effects on individuals' self-efficacy. [ABSTRACT FROM AUTHOR]

In this comment paper on von Fircks (2023a), I would like to focus on four issues and offer some reflections on them: first, what is happening in the process of a new I arising through mindfulness meditation practice? I would like to supplement the dialogue between Buber and Rogers in 1957 on the dynamism of I and Me, which is the basis of Mead's theory of self formation, in which I and Me separate, discover and meet a new self. The second, is that meditation, which at first glance appears to be an internal meditation practice and a personal activity, leads to a semiotic mediated social process. The Tao and early Buddhist ideas that form the background to the experiential process of mindfulness meditation will be reviewed, and the significance of people experiencing the interdependence of non-human nature and the environment through the practice will be discussed. Third, connecting this to the idea of Umwelt (Uexküll) and the semiosphere (Lotman), an attempt is made to extend the otherness as a collating body of self formation to Umwelt. Fourth, mindfulness meditation focuses attention on the breath. In relation to Mead's focus on the environment under the skin, i.e. corporeality, I will supplement the psychological meaning of cultivating the body's sense of interoception through the sensing of repetitive movements of tension and relaxation. Through the above, what kind of semiotic mediating function does mindfulness meditation have in relation to the construction of the new I, and how does it lead to the creation of social meaning? We would like to discuss these points. Clinical Trial Registration: The article does not contain any studies with clinical trial. This, clinical Trial registration is not applicable. [ABSTRACT FROM AUTHOR]

Background:Objective:Methods:Results:Conclusion:Trial registration:Fatigue is a common problem following the acute phase of COVID-19. Potential interventions to reduce fatigue and improve quality of life are appropriate.The study aimed to investigate the effect of auriculotherapy on persistent fatigue in recovered patients from acute phase COVID-19.This double-blind clinical trial was conducted in 2022 in Kashan, Iran on 52 recovered patients reporting persistent fatigue following acute phase COVID-19. A convenience sample was selected and randomly assigned to sham and intervention groups. The intervention group received four weeks of auriculotherapy with Vaccaria seeds attached to six fatigue-related auriculotherapy points on both ears. In the sham group, adhesive tapes were attached to the same points. Fatigue was assessed by the Chalder Fatigue Scale before (T0), after (T1), and four weeks after (T2) the intervention. Both per-protocol and intention-to-treat analyses were used.The two groups differed on financial status and hospitalization history (p < 0.05). The time-group interaction effect was significant for fatigue after adjusting for confounders (p < 0.0001). Fatigue scores of the intervention group were significantly lower than the sham group at T1 and T2 (p < 0.0001). In addition, fatigue scores in the intervention group decreased significantly over time, while in the sham group, fatigue first decreased briefly and then increased (p < 0.05).This initial trial suggested that auriculotherapy may reduce intensity of fatigue and therefore could potentially be integrated into rehabilitation programs for patients with prolonged COVID-19.Iranian Registry of Clinical Trials identifier: IRCT20100211003329N9. [ABSTRACT FROM AUTHOR]

Summary This paper first describes the difficulties in providing the required sample sizes for clinical trials that guarantee type 1 and type 2 error control. The required sample sizes obviously depend on the test employed, and in this study we use the so‐called E‐test, which is known to have extremely favourable size properties and higher power than alternatives. To compute exact powers for this test in real time is not currently feasible, so a corpus of pre‐computed exact powers (and sizes) was created, covering sample sizes up to 500. When there are no solutions within the corpus, a novel extrapolation technique is used. Exact size can be computed after the sample sizes have been extracted; however, for the E‐test the exact size is virtually always very close to the nominal target. All the code has been converted into an R‐package, which is available on CRAN and illustrated. [ABSTRACT FROM AUTHOR]